Analyzer

ABSTRACT

An object of the present invention relates to providing a nucleic acid analyzer capable of testing a plurality of test items in parallel, and of obtaining high efficiency of specimen processing even if the test item or a measuring object is changed. The present invention relates to an analyzer including a carousel rotatable about a rotation axis, a plurality of reaction containers held along a circumferential edge of the carousel, and at least one detector having a light source for irradiating the reaction container with excitation light and a detection element for detecting fluorescence from a reaction liquid in the reaction container. The detector is removable. By attaching a desired detector, it is possible to perform fluorescence measurement in response to the test item. According to the present invention, it is possible to test a plurality of test items in parallel, and even if the test item or the measuring object is changed, the high efficiency of specimen processing can be obtained.

TECHNICAL FIELD

The present invention relates to an analyzer for analyzing abiologically-related substance, and for example, relates to an analyzerfor analyzing nucleic acid.

BACKGROUND ART

As a nucleic acid amplification method, for example, the PCR method isknown. In the PCR method, nucleic acid contained in a specimen isamplified in a base sequence-specific manner to detect a trace ofnucleic acid with high sensitivity. Generally in the nucleic acidamplification method, a fluorophore is used for nucleic acid labeling,and changes in fluorescence intensity are chronologically tracked toperform an analysis. Additionally, in an amplification process,temperatures of a reaction liquid are controlled to facilitate areaction.

JP Patent Publication (Kokai) No. 2002-116148 A (Patent Document 1)discloses a fluorescence-type plate analyzing device in which reactioncontainers, each of which is referred to as a “well”, are arranged inlattice form on a quadrate plate. In this device, irradiation anddetection optical systems are provided on a bottom side of the plate.The plate is moved along a horizontal plane in longitudinal and lateraldirections, to detect fluorescence from a sample held in the well.Additionally, in this device, the fluorescence is detected not only at asingle detection position but also at a plurality of detection positionsto perform fluorescence measurement efficiently. Moreover, LEDs(Light-Emitting Diodes) are used as the excitation light source for thepurpose of providing a low-price and compact-size device in which it iseasy to maintain an excitation light source.

Patent Document 1: JP Patent Publication (Kokai) No. 2002-116148 ADISCLOSURE OF THE INVENTION Problems to be Solved by the Invention

The inventors of the present application have conducted concentratedstudies on a nucleic acid analyzer suitable for a clinical test, andfound knowledge as described below.

In the clinical test, there is a need to obtain test results withrespect to a plurality of test items from a specimen. In addition, forthe purpose of improving efficiency of testing items, it would beefficient if a plurality of test items could be processed in parallel.It is desirable to assign a different fluorophore to each of measuringobjects, as a marker of nucleic acid amplification. Besides, it isdesirable to measure two types of fluorophores of a measuring object andan internal standard respectively in parallel, in addition to setting aplurality of test items. Further, in a clinical test, the test items orthe measuring objects are frequently changed, increased, or decreased,and therefore it is required to be able to respond to an emergentmeasurement or test.

An object of the present invention is to provide a nucleic acid analyzercapable of testing a plurality of test items in parallel, and ofobtaining high efficiency of specimen processing even if a test item ora measuring object is changed.

Means for Solving the Problems

The present invention relates to an analyzer comprising a carouselrotatable about a rotation axis, a plurality of reaction containers heldalong a circumferential edge of the carousel, and at least one detectorincluding a light source for irradiating the reaction container withexcitation light and a detection element for detecting fluorescence froma reaction liquid in the reaction container. The detector is removable.By attaching a desired detector, it is possible to perform fluorescencemeasurement in response to a test item.

Effects of the Invention

According to the present invention, it is possible to test a pluralityof test items in parallel, and even if the test item or a measuringobject is changed, high efficiency of specimen processing can beobtained.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1A is an explanatory view showing a first example of across-sectional structure of a main part of an analyzer.

FIG. 1B is an explanatory view showing a second example of across-sectional structure of a main part of an analyzer.

FIG. 2 is an explanatory view showing an example of a planar structureof a main part of an analyzer.

FIG. 3 is an explanatory view showing a mechanism in which crosstalkoccurs between adjacent detectors in an analyzer.

FIG. 4A is an explanatory view showing a means for preventing crosstalkbetween adjacent detectors in a main part of an analyzer.

FIG. 4B is an explanatory view showing a means for preventing crosstalkbetween adjacent detectors in a main part of an analyzer.

FIG. 5A is an explanatory view showing an example of an optical systemof a detector of an analyzer.

FIG. 5B is an explanatory view showing an example of an optical systemof a detector of an analyzer.

FIG. 6 is an explanatory view showing an example of an array structureof a detector of an analyzer.

FIG. 7 is an explanatory view showing an example of peak wavelengths offluorophores.

FIG. 8 is an explanatory view showing another example of an arraystructure of a detector of an analyzer.

DESCRIPTION OF SYMBOLS

1 Reading unit2 Reaction container

3 Carousel

4 Driving mechanism

5 Detector 6 Slot 8 Casing 9 Gate 10 Fan

11 Heat source12 Temperature sensor13 Heat source14 Temperature sensor

15 Douser 16 Shutter

21 Light source

22 Condenser

23 Excitation filter24 Fluorescence filter

25 Photodiode

26 Dichroic mirror

BEST MODE FOR CARRYING OUT THE INVENTION

An embodiment discloses a nucleic acid analyzer comprising a carouselrotatable about a rotation axis, a plurality of reaction containers heldalong a circumferential edge of the carousel, and at least one detectorincluding a light source for irradiating the reaction container withexcitation light and a detection element for detecting fluorescence froma reaction liquid in the reaction container, wherein the detector isremovably attached, and the detectors are configured to performfluorescence measurement independently of one another.

Also, an embodiment discloses a nucleic acid analyzer wherein each of aplurality of detectors is configured to comprise a light source forgenerating excitation light having a wavelength different from oneanother and a detection element for detecting fluorescence having awavelength different from one another.

Additionally, an embodiment discloses a nucleic acid analyzer whereineach of a plurality of detectors is selected such that the differencebetween wavelengths of excitation lights generated by light sources ofthe adjacent two detectors is larger than a predetermined wavelengthdifference, and the difference between wavelengths of fluorescencesdetected by detection elements of the adjacent two detectors is largerthan a predetermined wavelength difference.

Moreover, an embodiment discloses a nucleic acid analyzer wherein eachof a plurality of detectors is configured to comprise a light source forgenerating excitation light having the identical wavelength and adetection element for detecting fluorescence having the identicalwavelength.

Besides, an embodiment discloses a nucleic acid analyzer whereinamplification gains with respect to output signals from a plurality ofdetectors are set to be different from one another.

Also, an embodiment discloses a nucleic acid analyzer whereinresolutions of output signals from a plurality of detectors are set tobe different from one another.

Additionally, an embodiment discloses a nucleic acid analyzer wherein adouser is provided between adjacent two detectors of a plurality ofdetectors.

Moreover, an embodiment discloses a nucleic acid analyzer configuredsuch that a detector is provided with an openable and closable shutter;and when the detector optically detects a reaction solution in areaction container, the shutter opens; and when the detector does notoptically detect the reaction solution in the reaction container, theshutter closes.

Besides, an embodiment discloses a nucleic acid analyzer wherein a lightsource of a detecting device comprises a light-emitting diode, and adetection element comprises a photodiode.

Also, an embodiment discloses a nucleic acid analyzer comprising a slotfor removably supporting a detector; and configured such that thedetector can be removed or attached by moving the detector along theslot.

Additionally, an embodiment discloses a nucleic acid analyzer whereinthere is provided a temperature controlling device for keepingtemperatures of a reaction container and a reaction liquid in thereaction container at predetermined temperatures.

Moreover, an embodiment discloses a nucleic acid analyzer wherein atemperature controlling device comprises a fan, a heat source, and atemperature sensor.

Besides, an embodiment discloses a nucleic acid analyzer wherein atemperature controlling device comprises a heat source and a temperaturesensor which are provided in a carousel.

Also, an embodiment discloses a nucleic acid analyzer wherein there isprovided a casing for accommodating at least a carousel and a reactioncontainer; the casing comprises an openable and closable gate; and thereaction container can be taken in and out via the gate.

Additionally, an embodiment discloses a nucleic acid analyzer comprisinga carousel rotatable about a rotation axis, a plurality of reactioncontainers held along a circumferential edge of the carousel, at leastone detector including a light source for irradiating the reactioncontainer with excitation light and a detection element for detectingfluorescence from a reaction liquid in the reaction container, and atemperature controlling device for keeping temperatures of a reactioncontainer and a reaction liquid in the reaction container atpredetermined temperatures, wherein the detector is removably attached,and the detectors are configured to perform fluorescence measurementindependently of one another.

Moreover, an embodiment discloses a nucleic acid analyzer configuredsuch that a carousel is operated based on a cycle consisting of acontainer setting period for stopping the carousel in order to place orremove a reaction container and a fluorescence measurement period forrotating the carousel at a constant speed; and in the fluorescencemeasurement period, the detector measures fluorescence intensity whenthe reaction container is passing a detection position on a detector.

Besides, an embodiment discloses a nucleic acid analyzing method foranalyzing nucleic acid using a carousel rotatable about a rotation axis,wherein a plurality of reaction containers are placed along acircumferential edge of the carousel; a plurality of detectors placedalong an outer circumference of the carousel measure fluorescence from areaction solution contained in the reaction container while rotating thecarousel, each of the plurality of detectors performing fluorescencemeasurement of a predetermined reaction solution independently of oneanother; and when the number or type of reaction containers is to bechanged, the detector is added or removed.

Also, an embodiment discloses a nucleic acid analyzing method wherein aplurality of detectors detect fluorescence having wavelengths differentfrom one another.

Hereinafter, above-mentioned and other novel features and effects of thepresent invention will be described with reference to the drawings. Itis to be noted that the drawings are used exclusively for theunderstanding of the present invention, and by no means limit the scopeof right.

EMBODIMENTS

With reference to FIG. 1A, FIG. 1B, and FIG. 2, an example of a readingunit, which is a main part of an analyzer, will be described. A readingunit 1 of the present example includes a plurality of reactioncontainers 2 for accommodating reaction liquids which are targets foranalysis, a carousel 3 for holding the reaction containers 2, a drivingmechanism 4 for rotating the carousel, at least one detector 5 arrangedalong a circumference of the carousel 3, and a casing 8.

The carousel 3 includes a circular plate-shaped disk made of aluminumalloy, and is rotatable about a central axis. On an edge of the carousel3, the numerous reaction containers 2 are held. The detectors 5 arearranged along the circumference of the carousel 3 at regular intervals.The detectors 5 are arranged beneath the reaction container 2. In theexample of FIG. 1A, the detectors 5 are provided outside of the casing8. However, in the example of FIG. 1B, the detectors 5 are providedinside of the casing 8. Here, five detectors 5 are provided. However,any number of detectors 5 other than five may be provided.

The detector 5 is exchangeable, and is freely attached and removed. Thedetector 5 is inserted into a slot 6. The slot 6 may be configured so asto extend along a radial direction as the example shown in FIG. 1A.However, the slot 6 may be configured so as to extend along an axialdirection as the example shown in FIG. 1B. Further, although notillustrated, the slot 6 may be arranged to be inclined with respect tothe axial direction. That is, the slot 6 may be arranged along a conicalsurface. The detector 5 may be mounted by moving the detector 5 inwardlyalong the slot 6 as shown by an arrow 6A. The detector 5 may be removedby moving the detector 5 outwardly along the slot 6 in a directionopposite to the direction of the arrow 6A. In the slot 6, a snap-typefastening device may be provided. As shown by the arrow 6A, when thedetector 5 is moved along the slot 6 inwardly, the detector 5 engageswith the fastening device at a predetermined position, and cannot bemoved any more. When the detector 5 is to be removed, the fasteningdevice is released. The detector 5 may be fixed by a screw in place ofthe fastening device.

According to the present example, the detectors 5 can detect or measurethe reaction liquids in the reaction containers 2 independently of oneanother. Accordingly, in the case where one of detectors goes out oforder or maintenance of a detector is required, it is required to removeonly the detector. In this case, the remaining detectors can be usedwithout change. That is, no special tasks with respect to the remainingdetectors are required. Removal of the detector does not affectdetection sensitivity in the remaining detectors. Accordingly, it ispossible to make test results coincident with each other before andafter the tasks.

As shown in FIG. 1A and FIG. 1B, the casing 8 of the present example isprovided with an openable and closable gate 9. It is to be noted that inFIG. 2, the casing 8 has been removed. At least, the reaction container2 and the carousel 3 are accommodated in the casing 8. By the casing 8being provided in this way, it is possible to keep a temperature in thecasing 8 constant. Further, by the casing 8 being provided, it ispossible to prevent irradiation of unnecessary light to the reactioncontainer 2, and furthermore, to prevent incidence of unnecessary lightinto the detector 5. When the reaction container 2 is mounted to thecarousel 3, the mounting is performed via the gate 9. Accordingly, whenthe reaction container 2 is mounted, it is not required to remove awhole of the casing 8.

The reading unit 1 of the present example further includes a temperaturecontrolling device for keeping the temperature of the reaction liquidaccommodated in the reaction container 2 at a predetermined temperature.The temperature controlling device of the present example includes a fan10, a heat source 11, and a temperature sensor 12. The fan 10, the heatsource 11, and the temperature sensor 12 are provided near a ceiling ofthe casing 8. Similarly, the carousel 3 may also be provided with theheat source 13 and the temperature sensor 14.

Since air in the casing 8 is circulated by the fan 10, air stagnation ina specific area in the casing 8 is prevented. In particular, air aroundthe reaction container is circulated, and therefore air stagnationaround the reaction container is prevented. As the temperature sensors12 and 14, normal sensors may be used, each of which is configured so asto bring a thermosensor into contact with an object to be measured;however, a noncontact infrared thermometers may be used. The infraredthermometer enables noncontact temperature measurement of the reactioncontainer and the reaction liquid. Here, explanations have been made asto a first temperature controlling device provided near the ceiling ofthe casing 8 and a second temperature controlling device provided in thecarousel 3. According to the present invention, either of the firsttemperature controlling device or the second temperature controllingdevice may be provided, however, both of such devices may be provided.

The analyzer of the present example is applicable to analyzers forvarious specimens. However, here, an explanation will be made citing thenucleic acid analyzer as an example. Additionally, as an example of thereading unit, a case where the fluorescence is detected will bedescribed. The detector 5 includes an excitation light source forirradiating the reaction container 2 held by the carousel 3 withexcitation light. As this excitation light source, the light-emittingdiode (LED), a gas laser, a semiconductor laser, a xenon lamp, a halogenlamp, or the like may be used. However, as the excitation light source,the light-emitting diode is preferably used.

A sample solution containing fluorescence-labeled nucleic acid and thelike is held in the reaction container. When the reaction container 2 isirradiated with the excitation light from the excitation light source,the reaction liquid generates the fluorescence. The detector includes adetection element for detecting the fluorescence from the reactionliquid. As this detection element, a photodiode, a photomultiplier, CCD,or the like is used. However, as the detection element, the photodiodeis preferably used.

Temperature control for facilitating nucleic acid amplification includesperiodic control for changing temperatures cyclically and stepwisely asin the case of the PCR method, and constant-temperature control forkeeping a predetermined temperature for a predetermined period of timeas in the case of the NASBA method or the LAMP method. Further, in thecase where the nucleic acid analyzer is under a comparativelyhigh-temperature environment, an air conditioner is required. Thus, asthe heat sources 11 and 13, preferred are not only warming elements likeheaters but also temperature controlling elements with cooling functionssuch as Peltier elements.

An explanation will be made as to a case where the nucleic acid isamplified using the analyzer of the present example by means of anucleic acid amplification method. In the nucleic acid amplificationmethod, by taking fluorescent substances into synthetic productsquantitatively, it is possible to chronologically monitor the syntheticproducts. Here, an explanation will be made as to a case where the NASBAmethod, which is one of the nucleic acid amplification methods, isperformed. The NASBA method is one of constant-temperature amplificationmethods capable of amplification by use of only one temperature. In thepresent example, this temperature is 41 degrees. It is known that in thelight-emitting diode (LED) used as the excitation light source, due to achange in temperature of the LED itself, a peak wavelength and an amountof light are changed. Thus, both of the first temperature controllingdevice provided near the ceiling of the casing 8 and the secondtemperature controlling device provided in the carousel 3 are used, andtherefore it is possible to keep the temperature around thelight-emitting diode (LED) at 41 degrees. This makes it possible toeliminate unevenness of light-emitting characteristics of thelight-emitting diode (LED) and to hold the temperature of the reactioncontainer 2 at 41 degrees.

The reaction container 2 accommodates the reaction liquid containing aspecimen and a base labeled by the fluorescent substance. The reactioncontainers 2 are sequentially loaded into the carousel in apredetermined cycle, and the fluorescence measurement is performed.

An operational cycle of the carousel consists of the container settingperiod and the fluorescence measurement period. In the container settingperiod, the carousel is stopped, and the reaction container is placed orremoved. In the fluorescence measurement period, the fluorescencemeasurement is performed while rotating the carousel at a constantspeed. In the fluorescence measurement period, the fluorescenceintensity is measured when the reaction container is passing a detectionposition on the detector. The lengths of the container setting periodand the length of the fluorescence measurement period are constant, andthe setting and the measurement are repeated in a predetermined cycle.

Every time the carousel makes one rotation, the reaction containerpasses all of the detectors circumferentially placed. To each of thedetectors, the fluorescence of the wavelength to be measured has beenassigned. Each of the detectors independently detects the fluorescencehaving the wavelength assigned thereto. In each of the reactioncontainers 2, the identical specimen has been collected. Data measuredby each of the detectors is accumulated as a chronological change of thereaction liquid in an external computer, and further, is externallyoutput as a quantitative analytical result.

According to the present example, if a test item is newly developed, ora new fluorophore is adopted, the detector 5 is added or exchanged.Accordingly, even if the test items are increased, or the types of thefluorophore are changed, it is not required to introduce a new nucleicacid analyzer.

As mentioned above, normally, fluorescence measurements of thewavelengths different from one another are assigned to the detectorsrespectively. That is, the detectors each detect the fluorescences ofthe wavelengths being different from one another respectively. However,the identical wavelength may be assigned to the plurality of detectors.Here, an explanation will be made as to a case where the plurality ofdetectors measure the fluorescence having the identical wavelength.

First, an explanation will be made as to a method in which a measurementrange is optimized by giving a different gain to each detector. Forexample, the fluorescence having the identical wavelength is assigned toa first detector 5 a and a second detector 5 b. However, a configurationis made such that the gain of signal amplification in the first detector5 a is different from that in the second detector 5 b. That is, theamplification gains different from one another are given. This makes itpossible to optimize a range of the fluorescence intensity able to bemeasured. For example, the gain of the first detector 5 a is set to below, whereas the gain of the second detector 5 b is set to be high. Inthe case where the concentration of the specimen to which the nucleicacid amplification is performed is high, the fluorescence is detected bythe first detector 5 a. The first detector 5 a has a low gain andtherefore a high detection limit. Accordingly, even if the specimen hasa high concentration, the fluorescence can be detected. In the casewhere the concentration of the specimen is low, the fluorescence isdetected by the second detector 5 b. The second detector 5 b has a highgain and therefore a low detection limit. Accordingly, even if thespecimen has a low concentration, the fluorescence can be detected. Twodetectors detect the fluorescence having the identical wavelength.However, the two detectors have the different gains, and therefore, itis avoided that the fluorescence cannot be detected because thefluorescence is beyond the detection limit. That is, the measurementrange can be optimized by changing the gain for each detector. Thismakes it possible to lower a risk of wasting the specimen.

In order to give a different gain for each detector, a different gainmay be given to each signal amplifier which is placed after the outputsignal from detector is converted into a voltage signal. However, evenif a different detection element such as a photodiode or aphotomultiplier is incorporated in each of the detectors, the similarresult can be obtained.

Next, an explanation will be made as to a method in which the resolutionis optimized by giving a different bit resolution to each detector. Forexample, an A/D convertor of the first detector 5 a has the resolutionof 8 bits, whereas the A/D convertor of the second detector 5 b has theresolution of 16 bits. The 8 bits is a low resolution on the assumptionthat the specimen has the normal concentration. The 16 bits is a highresolution on the assumption that the specimen has a low concentration.Since in this way, the fluorescence of the specimen having a normalconcentration is assigned to the first detector 5 a and the fluorescenceof the specimen having a low concentration is assigned to the seconddetector 5 b, it is possible to detect a minute difference inconcentration.

As a method for giving a different bit resolution to each detector, adifferent bit resolution may be given to the A/D convertor for eachdetector. However, the number of integration of the obtained data may bechanged for each detector.

Further, to a plurality of detectors, the identical wavelengths may beassigned, and the identical amplification gains may be given. In thiscase, the identical detection result can be obtained from a plurality ofdetectors. However, resistance to a failure or a device error increases.In the present example, in the reaction containers placed in thecarousel 3, the identical specimens have been collected. Accordingly, ifthe reaction container or the detector is changed, only the effect dueto this change can be reflected on an analytical result, resulting in animprovement in reliability of measurement data.

Here, the explanation has been made citing the nucleic acid analyzer asthe example. However, the present invention is by no means limited tothe nucleic acid analyzer, and is applicable to devices for analyzingthe specimens collected from biological bodies at large. In addition,the explanation has been made as to the case where fluorescencedetection is performed as the example of the reading unit. However, thepresent invention is applicable also to the case where the target foranalysis is detected by means of methods other than the fluorescencedetection.

With reference to FIG. 3, an explanation will be made as to crosstalk.In the case where a plurality of fluorophores are detected, mixture ofthe fluorescence between adjacent detectors is highlighted as a problem.This crosstalk causes the S/N ratio to be lowered in the nucleic acidanalyzer which performs the fluorescence measurement. It is assumed thatwhen the first detector 5 a detects the fluorescence from the firstreaction container 2 a, the second detector 5 b simultaneously detectsthe fluorescence from the second reaction container 2 b.

The crosstalk detected by the first detector 5 a will be considered. Ifthe first detector 5 a detects fluorescence 301 from the adjacent secondreaction container 2 b, it causes the crosstalk. If the first reactioncontainer 2 a is irradiated with the excitation light 302 from theadjacent second detector 5 b, it generates the fluorescence. If thisfluorescence is detected by the first detector 5 a, it causes thecrosstalk.

With reference to FIG. 4A and FIG. 4B, an explanation will be made as toa means for preventing the crosstalk by means of the present invention.In an example shown in FIG. 4A, a douser 15 is provided between thefirst detector 5 a and the second detector 5 b. The douser 15 preventsthe fluorescence 301 from the adjacent second reaction container 2 bfrom reaching the first detector 5 a, and further, prevents the firstreaction container 2 a from being irradiated with the excitation light302 from the adjacent second detector 5 b. In an example shown in FIG.4B, each of the detectors 5 a and 5 b is provided with a shutter 16. Theshutter 16 is configured so as to block an excitation-light irradiationport or a fluorescence reading port of the detector. The shutter 16provides a function similar to the function of the douser 15.

The shutter 16 may be configured so as to be closed when the reactioncontainer, the fluorescence of which is not to be measured, is locatedat the detection position, and be opened when the reaction container,the fluorescence of which is to be measured, is located at the detectionposition. Further, as shown in FIG. 4B, a distance L between adjacenttwo detecting devices may be made sufficiently large. This makes itpossible to obtain the function similar to that of the douser 15 or theshutter 16. That is, the fluorescence 301 from the adjacent secondreaction container 2 b is prevented from reaching the first detector 5a. Further, the first reaction container 2 a is prevented from beingirradiated with the excitation light 302 from the adjacent seconddetector 5 b. It is to be noted that an interval between the adjacentreaction containers 2 a and 2 b may be made large. However, if theinterval L between the reaction containers 2 a and 2 b is too large, thenumber of reaction containers to be placed in the carousel decreases.Accordingly, the interval L between the reaction containers 2 a and 2 bis in a predetermined range.

Here, as the means for preventing the crosstalk, the douser 15, theshutter 16, and the case where the distance L between the two detectingdevices is made large have been explained. Some of these three means maybe appropriately combined.

With reference to FIG. 5A, an explanation will be made as to a firstexample of an optical system of the detector 5. The optical systemincludes an excitation optical system and a detection optical system.The excitation optical system includes a light source 21, condensers 22,and an excitation filter 23. The detection optical system includes thecondensers 22, a fluorescence filter 24, and a photodiode 25. In thepresent example, the bottom surface of the reaction container 2 isirradiated with the excitation light, and the fluorescence is detectedfrom a reading port opened on a side of the reaction container 2. It isto be noted that in the example of FIG. 5A, the shutter 16 which isshown in FIG. 4B is not illustrated, however, the shutter 16 may beprovided.

With reference to FIG. 5B, an explanation will be made as to a secondexample of the optical system of the detector 5. The optical systemincludes the excitation optical system, the detection optical system, adichroic mirror 26, and the shutter 16. The excitation optical systemincludes the light source 21, the condensers 22, and the excitationfilter 23. The detection optical system includes the condensers 22, thefluorescence filter 24, and the photodiode 25.

With reference to FIG. 6 and FIG. 7, an explanation will be made as toanother example of the means for preventing the crosstalk. As shown inFIG. 6, four detectors 5 a, 5 b, 5 c, and 5 d are sequentially arrangedin parallel along the circumference of the carousel 3. According to thepresent example, these detectors are selected such that a difference inwavelengths of the excitation light generated by the light sources ofthe two detectors adjacent with each other is larger than apredetermined difference in wavelengths. Further, these detectors areselected such that a difference in wavelengths of the fluorescencedetected by the detection elements of the two detectors adjacent witheach other is larger than a predetermined difference in wavelengths.Here, detected is the fluorescence from four fluorophores of FAM, ROX,Cy5, and Alexa405. FIG. 7 shows the wavelength of the excitation lightand the wavelength of the fluorescence of the respective fourfluorophores of FAM, ROX, Cy5, and Alexa405. Two peaks 701 near thewavelength 400 nm represent an absorption wavelength and a radiationwavelength of the fluorophore Alexa405. Two peaks 702 near thewavelength of 500 nm represent the absorption wavelength and theradiation wavelength of the fluorophore FAM. Two peaks 703 near thewavelength of 600 nm represent the absorption wavelength and theradiation wavelength of the fluorophore ROX. Two peaks 704 near thewavelength of 650 to 700 nm represent the absorption wavelength and theradiation wavelength of the fluorophore Cy5. Especially between the twofluorophores of FAM and ROX, and between the two fluorophores of ROX andCy5, the crosstalks are large. Thus, the detectors of the twofluorophores are arranged so as not to be adjacent with each other. Forexample, the fluorophore ROX may be assigned to the first detector 5 a;the fluorophore Alexa405 to the second detector 5 b; the fluorophore Cy5to the third detector 5 c; and the fluorophore FAM to the forth detector5 d. The assignments other than the above-mentioned assignments may bemade, if the detectors with respect to the two fluorophores of FAM andROX are not adjacent, and the detectors with respect to the twofluorophores of ROX and Cy5 are not adjacent.

With reference to FIG. 8, an explanation will be made as to an exampleof a means for improving reliability of the analytical result. Reagents,consumable items, and the like for the nucleic acid amplification usedin the nucleic acid analyzer generally have higher prices and highercontamination risks, compared with those in a biochemical or immunedevice. Thus, required is the higher reliability with respect to theanalytical result.

In the present example, as shown in FIG. 8, eight detectors 5 a, 5 b, 5c, 5 d, 5 e, 5 f, 5 g, and 5 h are sequentially arranged in parallelalong the circumference of the carousel 3. In the present example, thedetectors 5 a, 5 b, 5 c, and 5 d of a first group have theconfigurations identical to those of the detectors 5 e, 5 f, 5 g, and 5h of a second group. That is, each of pairs of the detectors arranged atboth ends of a diameter of the carousel 3 has the identicalconfiguration. For example, the first detector 5 a and the fifthdetector 5 e have the identical configuration, which generates theexcitation light having the identical wavelength and detects thefluorescence having the identical wavelength. Similarly, the seconddetector 5 b and the sixth detector 5 f have the identicalconfiguration, which generates the excitation light having the identicalwavelength and detects the fluorescence having the identical wavelength.The third detector 5 c and the seventh detector 5 g have the identicalconfiguration, which generates the excitation light having the identicalwavelength and detects the fluorescence having the identical wavelength.The forth detector 5 d and the eighth detector 5 h have the identicalconfiguration, which generates the excitation light having the identicalwavelength and detects the fluorescence having the identical wavelength.When the carousel 3 makes one rotation, two of the measurement data bymeans of the pair of detectors are obtained for each of the fluorophoresof the reaction liquid in each of the reaction containers. Themeasurement data obtained by the pair of detectors should be identical.For example, the identical measurement results should be obtained by thefirst detector 5 a and the fifth detector 5 e. If the identicalmeasurement results are not obtained, it is determined that thedetectors are under abnormal conditions, or it is determined thatprocessing such as data processing or display processing is underabnormal conditions. If the cause of the abnormal conditions is foundout and it is found that one of the pair of detectors is out of order,it is possible to determine that the other of detectors is under normalconditions. In this case, the measurement data from the detector whichis determined to be under normal conditions is adopted, and therefore itis possible to eliminate a need for performing the measurement again.Thus, it is possible to output the analytical results without wastingthe valuable specimen.

In the present example, the data at two points with respect to theidentical sample can be obtained. Thus, by creating an approximationcurve from a lot of data points, it is possible to improve precision ofthe approximation curve. Therefore, the analytical results having highprecision can be obtained.

Further, in the pair of detectors corresponding to each other betweenthe first group of the detectors 5 a, 5 b, 5 c, and 5 d, and the secondgroup of the detectors 5 e, 5 f, 5 g, and 5 h, it is assumed that one ofconstituent elements and measurement parameters is set to be different,and the other constituent elements and measurement parameters are madeidentical. If this leads to different results, it is possible todetermine that such results are attributed to the different constituentelement or measurement parameter.

In this way, it is possible to determine which of the constituentelements and the measurement parameters affects the measurement results,and which of them does not affect them. Further, with respect to theconstituent element or the measurement parameter which affects themeasurement results, it is possible to know how they affect suchresults.

As described above, the explanations have been made to the examples ofthe present invention. However, it will be readily understood by aperson skilled in the art that the present invention is by no meanslimited to the above-mentioned examples, and various modifications maybe made thereto in the scope of the invention recited in the appendedclaims.

1. A nucleic acid analyzer comprising a carousel rotatable about arotation axis, a plurality of reaction containers held along acircumferential edge of the carousel, and at least one detectorincluding a light source for irradiating the reaction container withexcitation light and a detection element for detecting fluorescence froma reaction liquid in the reaction container, wherein the detectors areremovably attached, and the detectors are configured to performfluorescence measurement independently of one another.
 2. The nucleicacid analyzer according to claim 1, wherein each of the plurality ofdetectors is configured to comprise a light source for generatingexcitation light having a wavelength different from one another and adetection element for detecting fluorescence having a wavelengthdifferent from one another.
 3. The nucleic acid analyzer according toclaim 1, wherein each of the plurality of detectors is selected suchthat a difference between wavelengths of excitation lights generated bylight sources of the adjacent two detectors is larger than apredetermined wavelength difference, and a difference betweenwavelengths of fluorescences detected by detection elements of theadjacent two detectors is larger than a predetermined wavelengthdifference.
 4. The nucleic acid analyzer according to claim 1, whereineach of the plurality of detectors is configured to comprise a lightsource for generating excitation light having an identical wavelengthand a detection element for detecting fluorescence having an identicalwavelength.
 5. The nucleic acid analyzer according to claim 4, whereinamplification gains with respect to output signals from the plurality ofdetectors are set to be different from one another.
 6. The nucleic acidanalyzer according to claim 4, wherein resolutions of output signalsfrom the plurality of detectors are set to be different from oneanother.
 7. The nucleic acid analyzer according to claim 1, wherein adouser is provided between the adjacent two detectors of the pluralityof detectors.
 8. The nucleic acid analyzer according to claim 1, whereinthe detector is provided with an openable and closable shutter; and whenthe detector optically detects a reaction solution in the reactioncontainer, the shutter opens; and when the detector does not opticallydetect the reaction solution in the reaction container, the shuttercloses.
 9. The nucleic acid analyzer according to claim 1, wherein thelight source of the detecting device comprises a light-emitting diode,and the detection element comprises a photodiode.
 10. The nucleic acidanalyzer according to claim 1, comprising a slot for removablysupporting the detector, wherein by moving the detector along the slot,the detector can be removed or attached.
 11. The nucleic acid analyzeraccording to claim 1, wherein there is provided a temperaturecontrolling device for keeping temperatures of the reaction containerand a reaction liquid in the reaction container at predeterminedtemperatures.
 12. The nucleic acid analyzer according to claim 11,wherein the temperature controlling device comprises a fan, a heatsource, and a temperature sensor.
 13. The nucleic acid analyzeraccording to claim 11, wherein the temperature controlling devicecomprises a heat source and a temperature sensor which are provided inthe carousel.
 14. The nucleic acid analyzer according to claim 1,wherein there is provided a casing for accommodating at least thecarousel and the reaction container; the casing comprises an openableand closable gate; and the reaction container can be taken in and outvia the gate.
 15. A nucleic acid analyzer comprising a carouselrotatable about a rotation axis, a plurality of reaction containers heldalong a circumferential edge of the carousel, at least one detectorincluding a light source for irradiating the reaction container withexcitation light and a detection element for detecting fluorescence froma reaction liquid in the reaction container, and a temperaturecontrolling device for keeping temperatures of the reaction containersand the reaction liquids in the reaction containers at predeterminedtemperatures, wherein the detector is removably attached, and thedetectors are configured to perform fluorescence measurementindependently of one another.
 16. The nucleic acid analyzer according toclaim 15, comprising a slot for removably supporting the detector,wherein by moving the detector along the slot, the detector can beremoved or attached.
 17. The nucleic acid analyzer according to claim15, wherein the carousel is operated based on a cycle consisting of acontainer setting period for stopping the carousel in order to place orremove the reaction container and a fluorescence measurement period forrotating the carousel at a constant speed; and in the fluorescencemeasurement period, the detector measures fluorescence intensity whenthe reaction container is passing a detection position on the detector.18. A nucleic acid analyzing method for analyzing nucleic acid using acarousel rotatable about a rotation axis, wherein a plurality ofreaction containers are placed along a circumferential edge of thecarousel; a plurality of detectors placed along an outer circumferenceof the carousel measure fluorescence from a reaction solution containedin the reaction container while rotating the carousel, each of theplurality of detectors performing fluorescence measurement of apredetermined reaction solution independently of one another; and whenthe number or type of the reaction containers is changed, the detectoris added or removed.
 19. The nucleic acid analyzing method according toclaim 18, wherein the plurality of detectors detect fluorescence havingwavelengths different from one another.